The immotile cilia syndromes (ICS) are a genetically determined set of disorders characterized by dysmotility or immotility of the cilia in airway epithelial cells, spermatozoa and other ciliated cells of the body. Kartagener syndrome (KS) is a subgroup of ICS characterized by a classic triad of symptoms: situs inversus, bronchiectasis and chronic sinusitis. Ciliary immotility is caused by various ultrastructural defects of cilia, predominantly by a lack of dynein arms. The clinical consequences of KS include pronounced craniofacial manifestations. In 1994, we initiated a large-scale collaborative genetic epidemiology study of KS with Dr. Michal Witt of Poznan, Poland. Polish families with at least one child affected with KS are being recruited for this study. Coded DNA samples and research medical records are being sent to our laboratory for genotyping and statistical analyses using linkage and linkage disequilibrium approaches. We use microsatellite markers and fluorescence-based automated DNA fragment analysis hardware and software. During the past year we have completed statistical analyses of most of the human genome (ca. 90 percent) and have found one location with a LOD score greater than 3.0. This nearly reaches the currently accepted threshold of 3.3 or 3.6 sufficient for statistically significant mapping of the KS disease locus. Pending confirmation of this finding, we will next consider evaluating candidate genes known to map within this chromosomal region. We have been working to further assess the finding using a second set of KS families from Poland and these data have been processed in our laboratory and are being statistically analyzed. Our evidence indicates that KS may be genetically heterogeneous, with more than a single locus underlying the disease, and so we are continuing to collect additional families and perform additional gene mapping molecular and statistical analyses with the goal of identifying these additional genes. We plan to complete our laboratory and statistical assessment of an ongoing genome scan for KS susceptibility genes, to continue to recruit additional study subjects in Poland, and to evaluate candidate genes in the chromosomal location identified as noted above.